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Summary

Altered ion channel activity is linked to cancer and vascular malformations. This study identified specific ion channel genes with altered expression in tumors and electrophysiological changes in vascular malformations, suggesting diagnostic potential.

Keywords:
Autonomic nervous systemCancerFlat port-wine stainsIon-channelsSSRSympathetic skin response

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Area of Science:

  • Oncology
  • Molecular Biology
  • Physiology

Background:

  • Cellular functions, including angiogenesis and cell death, depend on transmembrane voltage control.
  • Altered ion transport may contribute to abnormal angiogenesis in cancers and vascular malformations.

Purpose of the Study:

  • To investigate the association between ion channel alterations and the development of solid tumors and vascular malformations.
  • To identify specific ion channel genes with altered expression in various human cancers.
  • To assess electrophysiological changes in vascular malformations.

Main Methods:

  • Analyzed expression of 90 ion channel genes in human solid tumor biopsies from 3673 patients across five cancer types using the Oncomine database.
  • Measured in vivo sympathetic skin responses (SSR) in 14 patients with port-wine stains to assess ion channel activity.

Main Results:

  • Significantly increased expression of several ion channels was observed in tumors (p < 0.0005).
  • Nine specific ion channel genes (CACNA1D, FXYD3, FXYD5, HTR3A, KCNE3, KCNE4, KCNN4, CLIC1, TRPM3) showed significant modification in at least half of the datasets for each cancer type.
  • In vivo studies revealed significantly reduced SSR in port-wine stain affected skin compared to healthy skin (p < 0.05).

Conclusions:

  • Identified ion channel genes with significantly modified expression in tumors and cancer-associated vasculature.
  • Demonstrated relevant electrophysiological alterations in human vascular malformations.
  • Suggests a potential diagnostic role for ion-electron transport in vascular disorders underlying tumor angiogenesis and malformations.